Effect of multimeric structure of the factor VIII/von Willebrand factor protein on binding to platelets.
The characteristics of the intact factor VIII/von Willebrand factor protein binding to human platelets was compared to 2-mercaptoethanol-treated factor VIII/von Willebrand factor protein and to fractions of plasma factor VIII/von Willebrand factor protein that elute after the void volume. These studies indicate that the factor VIII/von Willebrand factor protein larger size oligomers bind preferentially with high affinity to low capacity sites on human platelets. The intermediate and smaller size oligomers bind with intermediate or low affinity to sites with a much greater capacity. The results from binding analysis are also paralleled by the competitive inhibition of the intact factor VIII/von Willebrand factor protein by the various 2-mercaptoethanol-treated materials. These studies indicate that the two classes of binding sites seen in previous reports of factor VII/von Willebrand factor binding reflect heterogeneity in the oligomer size of the factor VIII/von Willebrand factor protein used in these assays. This study provides a model for understanding some of the normal structure-function relationships of the normal factor VIII/von Willebrand factor protein and the defect(s) in a variant form of von Willebrand's disease. In this form of the disease, decreased factor VIII/von Willebrand factor binding to platelets is reflected in decreased von Willebrand factor activity but coagulant and/or antigen levels are normal or only slightly decreased.
D000818:Animals; D001667:Binding, Competitive; D001779:Blood Coagulation Factors; D001792:Blood Platelets / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005169:Factor VIII; D006041:Goats; D006801:Humans; D008623:Mercaptoethanol / Q000494:pharmacology; D008970:Molecular Weight; D011108:Polymers; D011485:Protein Binding; D013997:Time Factors; D014841:von Willebrand Factor
D001779:Blood Coagulation Factors; D011108:Polymers; D014841:von Willebrand Factor; D008623:Mercaptoethanol; D005169:Factor VIII